Visual processing of words in a patient with visual form agnosia: A behavioural and fMRI study

Patient D.F. has a profound and enduring visual form agnosia due to a carbon monoxide poisoning episode suffered in 1988. Her inability to distinguish simple geometric shapes or single alphanumeric characters can be attributed to a bilateral loss of cortical area LO, a loss that has been well established through structural and functional fMRI. Yet despite this severe perceptual deficit, D.F. is able to “guess” remarkably well the identity of whole words. This paradoxical finding, which we were able to replicate more than 20 years following her initial testing, raises the question as to whether D.F. has retained specialized brain circuitry for word recognition that is able to function to some degree without the benefit of inputs from area LO. We used fMRI to investigate this, and found regions in the left fusiform gyrus, left inferior frontal gyrus, and left middle temporal cortex that responded selectively to words. A group of healthy control subjects showed similar activations. The left fusiform activations appear to coincide with the area commonly named the visual word form area (VWFA) in studies of healthy individuals, and appear to be quite separate from the fusiform face area. We hypothesize that there is a route to this area that lies outside area LO, and which remains relatively unscathed in D.F

Manual for starch gel electrophoresis: A method for the detection of genetic variation

The procedure to conduct horizontal starch gel electrophoresis on enzymes is described in detail. Areas covered are (I) collection and storage of specimens, (2) preparation of tissues, (3) preparation of a starch gel, (4) application of enzyme extracts to a gel, (5) setting up a gel for electrophoresis, (6) slicing a gel, and (7) staining a gel. Recipes are also included for 47 enzyme stains and 3 selected gel buffers. (PDF file contains 26 pages.

Weight and see: Line bisection in neglect reliably measures the allocation of attention, but not the perception of length

Line bisection has long been a routine test for unilateral neglect, along with a range of tests requiring cancellation, copying or drawing. However, several studies have reported that line bisection, as classically administered, correlates relatively poorly with the other tests of neglect, to the extent that some authors have questioned its status as a valid test of neglect. In this article, we re-examine this issue, employing a novel method for administering and analysing line bisection proposed by McIntosh et al. (2005). We report that the measure of attentional bias yielded by this new method (EWB) correlates significantly more highly with cancellation, copying and drawing measures than the classical line bisection error measure in a sample of 50 right-brain damaged patients. Furthermore when EWB was combined with a second measure that emerges from the new analysis (EWS), even higher correlations were obtained. A Principal Components Analysis found that EWB loaded highly on a major factor representing neglect asymmetry, while EWS loaded on a second factor which we propose may measure overall attentional investment. Finally, we found that tests of horizontal length and size perception were related poorly to other measures of neglect in our group. We conclude that this novel approach to interpreting line bisection behaviour provides a promising way forward for understanding the nature of neglect

Motivated proteins: a web application for studying small three-dimensional protein motifs

<b>BACKGROUND:</b> Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns.We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. <b>DESCRIPTION:</b> The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. <b>CONCLUSION:</b> Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schem

Metalloproteinase and inhibitor expression profiling of resorbing cartilage reveals pro-collagenase activation as a critical step for collagenolysis

Excess proteolysis of the extracellular matrix (ECM) of articular cartilage is a key characteristic of arthritis. The main enzymes involved belong to the metalloproteinase family, specifically the matrix metalloproteinases (MMPs) and a group of proteinases with a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS). Chondrocytes are the only cell type embedded in the cartilage ECM, and cell-matrix interactions can influence gene expression and cell behaviour. Thus, although the use of monolayer cultures can be informative, it is essential to study chondrocytes encapsulated within their native environment, cartilage, to fully assess cellular responses. The aim of this study was to profile the temporal gene expression of metalloproteinases and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), reversion-inducing cysteine-rich protein with Kazal motifs (RECK), and α(2)-macroglobulin (α(2)M), in actively resorbing cartilage. The addition of the pro-inflammatory cytokine combination of interleukin-1 (IL-1) + oncostatin M (OSM) to bovine nasal cartilage induces the synthesis and subsequent activation of pro-metalloproteinases, leading to cartilage resorption. We show that IL-1+OSM upregulated the expression of MMP-1, -2, -3, -9, 12, -13, -14, TIMP-1, and ADAMTS-4, -5, and -9. Differences in basal expression and the magnitude of induction were observed, whilst there was no significant modulation of TIMP-2, -3, RECK, or ADAMTS-15 gene expression. IL-1+OSM downregulated MMP-16,TIMP-4, and α(2)M expression. All IL-1+OSM-induced metalloproteinases showed marked upregulation early in the culture period, whilst inhibitor expression was reduced throughout the stimulation period such that metalloproteinase production would be in excess of inhibitors. Moreover, although pro-collagenases were upregulated and synthesized early (by day 5), collagenolysis became apparent later with the presence of active collagenases (day 10) when inhibitor levels were low. These findings indicate that the activation cascades for pro-collagenases are delayed relative to collagenase expression, further confirm the coordinated regulation of metalloproteinases in actively resorbing cartilage, and support the use of bovine nasal cartilage as a model system to study the mechanisms that promote cartilage degradation

A stated preference investigation of household demand for illegally hunted bushmeat in the Serengeti, Tanzania

This paper originates in a research project “Hunting for Sustainability” supported by the European Commission under the 7th Framework Programme for Research and Technological Development, and the research has been co-funded by Frankfurt Zoological Society.Illegal hunting for bushmeat is regarded as an important cause of biodiversity decline in Africa. We use a ‘stated preferences’ method to obtain information on determinants of demand for bushmeat and two other protein sources, fish and chicken, in villages around the Serengeti National Park, Tanzania. Our study focuses particularly on the impact of price changes, as anticipating and understanding the impact of price changes (whether caused by conservation interventions or market changes) on demand for bushmeat enables effective responses to be planned. We estimate the effects of changes in the price of bushmeat and in the prices of two substitute protein sources – fish and chicken – on household demand for bushmeat. Results suggest that increasing the availability of lower priced protein substitutes would reduce demand for bushmeat, and therefore, potentially pressure on wildlife populations. However, raising the price of bushmeat (e.g. as a result of reducing illegal hunting) would reduce household demand to a greater degree than equivalent decreases in the price of alternative protein sources. In both cases, elasticity of demand parameters are reported, which summarize the relative response to households to these alternative interventions. A 10% rise in bushmeat prices would reduce demand by around 6–7%, while a 10% fall in chicken or fish prices would reduce bushmeat demand by around 3–4%. The response to price changes varied between ethnic groups, and also according to household size (with the direction of the effect depending on whether the substitute was chicken or fish), but was not significantly affected by wealth or income.PostprintPeer reviewe

A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist

The overarching trend in mitochondrial genome evolution is functional streamlining coupled with gene loss; therefore, gene acquisition by mitochondria is considered to be exceedingly rare. Selfish elements in the form of self-splicing introns occur in many organellar genomes, but the wider diversity of selfish elements, and how they persist in the DNA of organelles, has not been explored. In the mitochondrial genome of a marine heterotrophic katablepharid protist, we identify a functional type II restriction modification (RM) system originating from a horizontal gene transfer (HGT) event involving bacteria related to flavobacteria. This RM system consists of an HpaII-like endonuclease and a cognate cytosine methyltransferase (CM). We demonstrate that these proteins are functional by heterologous expression in both bacterial and eukaryotic cells. These results suggest that a mitochondrial-encoded RM system can function as a toxin-antitoxin selfish element and that such elements could be co-opted by eukaryotic genomes to drive biased organellar inheritance.Peer reviewe

Pseudo-prospective Evaluation of UCERF3-ETAS Forecasts During the 2019 Ridgecrest Sequence

The 2019 Ridgecrest sequence provides the first opportunity to evaluate Uniform California Earthquake Rupture Forecast v.3 with epidemic‐type aftershock sequences (UCERF3‐ETAS) in a pseudoprospective sense. For comparison, we include a version of the model without explicit faults more closely mimicking traditional ETAS models (UCERF3‐NoFaults). We evaluate the forecasts with new metrics developed within the Collaboratory for the Study of Earthquake Predictability (CSEP). The metrics consider synthetic catalogs simulated by the models rather than synoptic probability maps, thereby relaxing the Poisson assumption of previous CSEP tests. Our approach compares statistics from the synthetic catalogs directly against observations, providing a flexible approach that can account for dependencies and uncertainties encoded in the models. We find that, to the first order, both UCERF3‐ETAS and UCERF3‐NoFaults approximately capture the spatiotemporal evolution of the Ridgecrest sequence, adding to the growing body of evidence that ETAS models can be informative forecasting tools. However, we also find that both models mildly overpredict the seismicity rate, on average, aggregated over the evaluation period. More severe testing indicates the overpredictions occur too often for observations to be statistically indistinguishable from the model. Magnitude tests indicate that the models do not include enough variability in forecasted magnitude‐number distributions to match the data. Spatial tests highlight discrepancies between the forecasts and observations, but the greatest differences between the two models appear when aftershocks occur on modeled UCERF3‐ETAS faults. Therefore, any predictability associated with embedding earthquake triggering on the (modeled) fault network may only crystalize during the presumably rare sequences with aftershocks on these faults. Accounting for uncertainty in the model parameters could improve test results during future experiments.Maximilian J. Werner and Warner Marzocchi received funding from the European Union's Horizon 2020 research and innovation program (Number 821115, RISE: Real‐Time Earthquake Risk Reduction for a Resilient Europe). This research was supported by the Southern California Earthquake Center (SCEC; Contribution Number 10082). SCEC is funded by National Science Foundation (NSF) Cooperative Agreement EAR‐1600087 and the U.S. Geological Survey (USGS) Cooperative Agreement G17AC00047

The Influences of Reproductive Status and Acute Stress on the Levels of Phosphorylated Mu Opioid Receptor Immunoreactivity in Rat Hippocampus

Opioids play a critical role in hippocampally dependent behavior and plasticity. In the hippocampal formation, mu opioid receptors (MOR) are prominent in parvalbumin (PARV) containing interneurons. Previously we found that gonadal hormones modulate the trafficking of MORs in PARV interneurons. Although sex differences in response to stress are well documented, the point at which opioids, sex, and stress interact to influence hippocampal function remains elusive. Thus, we used quantitative immunocytochemistry in combination with light and electron microscopy for the phosphorylated MOR (pMOR) at the SER375 carboxy-terminal residue in male and female rats to assess these interactions. In both sexes, pMOR-immunoreactivity (ir) was prominent in axons and terminals and in a few neuronal somata and dendrites, some of which contained PARV in the mossy fiber pathway region of the dentate gyrus (DG) hilus and CA3 stratum lucidum. In unstressed rats, the levels of pMOR-ir in the DG or CA3 were not affected by sex or estrous cycle stage. However, immediately following 30 min of acute immobilization stress (AIS), males had higher levels of pMOR-ir whereas females at proestrus and estrus (high estrogen stages) had lower levels of pMOR-ir within the DG. In contrast, the number and types of neuronal profiles with pMOR-ir were not altered by AIS in either males or proestrus females. These data demonstrate that although gonadal steroids do not affect pMOR levels at resting conditions, they are differentially activated both pre and postsynaptic MORs following stress. These interactions may contribute to the reported sex differences in hippocampally dependent behaviors in stressed animals